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Cancer & the Immune System

Hugh B. Fackrell

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Cancer & the Immune System

Assigned Reading Content Outline Performance Objectives

– Key terms– Key Concepts

Short Answer Questions

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Assigned Reading Janis Kuby’s Immunology 4th Ed

Chapter: 22 pp 539-561 Janis Kuby’s Immunology 3rd Ed Chapter: 24 pp 573-596

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Content Outline Origins & Terms Malignant Transformation Tumours of the Immune System Tumour Antigens TATAs on human melanomas Immune Response to Tumours Tumour Evasion of Immune Response Cancer Immunotherapy

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Origins & Terms

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Benign vs malignant

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Distribution of Cancer

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Growth of Breast Cancer

Dia

mete

r of

Tu

mou

r (m

m)

Tumour Cell doubling

Tumour visible by X raysTumour first palpable

Death of Patient

108cells

109cells

1012cells

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Altered Growth Properties

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Localized Benign Tumour

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Tumour Invasion of Basal Lamina

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Metastasizes to Other Sites

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Tumour Antigens Tumour specific Antigens

– chemically induced– virally induced

Tumour associated antigens– oncofetal tumour antigens– oncogene proteins

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TSTA vs TATA

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Radio labelled anti CEA

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Genes for TSTAs

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Malignant Transformation Oncogenes Induction of cell proliferation Inhibition of cell proliferation Regulation of apoptosis

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Chromosomal translocations

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Tumour Induction

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Induction of Tumours

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Tumours of the Immune System

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TATAs on human melanomas

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TATAs on human melanomas

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Immunity to Polyoma virus(1)

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Immunity to Polyoma virus(2)

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Immunity to Polyoma virus (3)

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Immunity to Polyoma Virus (4)

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Immune Response to Tumours

NK cells & macrophages Immune surveillance theory

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Tumour Evasion of Immune Response

Immunologic enhancement Modulation of tumour antigens Reduce MHC-I No co-stimulatory signal

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Tumor Escape

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Cancer Immunotherapy Modify Co-stimulatory signal Enhance APC activity Cytokine therapy MABs Tumour cell vaccines

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Cancers Treatable by Bone Marrow Transplants

Allogenic/syngenic Transplant– Breast cancer– aplastic anemia– leukemia– ALL– CML– Myeolodysplasia– multiple myeloma– Non- Hodgkin’s lymphoma– Hodgkin’s disease

Autologous Transplants– Leukemia– AML– ALL– Multiple Myeloma– Non Hodgkin’s lymphoma– Hodkin’s disease– Solid tumours– Breast– ovarian– testicular– Neuroblastoma

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Transfect co stimulartory signal

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Transfect with GM-CSF

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Lak cells & IL-2

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Mabs to B cell Lymphoma

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Tumour Cell VaccineImmune Response to MCA or

PVTransplant killed cells

of MCA induced sarcoma A

Challenge with Sarcoma A- No Growth

Challenge with Sarcoma B- growth

Transplant killed cells of Polyoma Virus

induced sarcoma A Challenge with

sarcoma A no growth challenge with

sarcoma B no growth SV40 induced

sarcoma C- growth

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DONE!!!

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Performance Objectives

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Key Terms antibody dependent cell mediated

cytotoxicity (ADCC), benign tumour, cancer,

carcinogens, proto oncogens, immune surveillance, Specific immunotherapy,

non specific immunotherapy, immunotoxins,Lymphokine activated killer cell(LAK),

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neoplasm, oncofetal antigens, oncogens, tumour, tumour associated antigens,

tumour associated transplantation antigens, tumour specific antigens,

tumour specific transplantation antigens

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Key Concepts Differentiate between a benign tumour and a

malignant tumour. Describe the concept of immunosurveillance Describe the different ways that tumours

can camouflage themselves to evade immune defenses,

Discuss the advantages of immunotherapy over other forms of cancer therapy.

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Distinguish between specific and nonspecific immunotherapy with the use of specific examples.

Describe immunotoxins. Describe the development of humanized

antibodies to tumour antigens Evalulate the contribution of T cells, NK

cells, Macrophages, and B cells to tumour immunity.

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Distinguish between tumour specific transplantation antigens and tumour assoicated transplantation antigens.

Describe oncofetal antigens.

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Short Answer Questions

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Explain how some cancer cells that can make TGF-beta are immunosuppressive.

Tumours and transplants are similar to one another,yet very different. Explain this observation in the context of what the immune system recognizes and the result of this recognition.

The qualities of proliferation and differentiation are essentially all that distinguishes a normal cell from a cancer cell. Explain.

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Design an experiment using mice that proves that the immune system provides immunity against tumours.

Distinguish between tumour-specific transplantation antigens (TSTA) and tumour associated transplantation antigens (TATA).

Design an experiment to show Tumour associated Transplantation Antigens (TATA).

What is the main difference separating cell surface antigens from chemically induced and virually induced cancers?

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Speculate on why this difference leads to difficulty in designing anticancer vaccines.

What are oncofetal antigens? Are they important in tumour immunity? Why?

What is immune surveillance? All evidence for immune surveillance is

indirect. Speculate on how you could get direct evidence.

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What immune cells play a role in tumour rejection? Briefly describe how each accomplishes this task. Include such things as cytokines, perforins, ADCC etc.

Cancers camouflage themselves to evade antitumour defenses. Pick three possible forms of camouflage that you think are most important, describe them and state why you think they are most important.

What are immunotoxins?

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Surgery, radiation and chemotherapy are the methods most widely used to treat cancer patients. What are the problems with this regimen, and how could immunotherapy overcome these problems.

Distinguish between specific and nonspecific immunotherapy.